Astellas Pharma has dosed the first patient in a Phase 3 trial testing its investigational cancer drug setidegrasib in patients with previously treated, KRAS G12D-mutated advanced non-small cell lung cancer (NSCLC).

 

This, opening a late-stage test of a new approach to targeting one of the disease’s cancer-driving mutations.

 

The randomized study will compare setidegrasib with docetaxel in patients whose locally advanced or metastatic NSCLC has progressed following platinum-based chemotherapy and checkpoint inhibitor therapy.

 

The trial is designed to enroll about 356 patients across multiple countries. Its two primary endpoints are progression-free survival and overall survival, with progression-free survival assessed by blinded independent central review.

 

The move marks the second Phase 3 study of setidegrasib launched by Astellas within six months. The company began a separate Phase 3 trial of the drug in previously untreated pancreatic ductal adenocarcinoma in April.

 

KRAS G12D is a mutation found in about 5% of people with NSCLC. While targeted therapies have advanced treatment for some other molecularly defined forms of lung cancer, there are currently no therapies specifically approved for KRAS G12D-mutated NSCLC, according to Astellas and cited clinical literature.

 

For patients whose disease progresses after initial treatment, treatment options include standard systemic therapies such as chemotherapy.

 

Setidegrasib is designed to take a different approach: rather than simply blocking KRAS G12D activity, the investigational drug is intended to trigger the selective degradation and removal of the cancer-driving protein using the cell’s own protein-degradation machinery.

 

Hidenori Kitai, of Hokkaido University, said the new trial addresses a significant treatment gap for patients whose disease has progressed after standard therapies.

 

“For too long, patients with KRAS G12D-mutated non-small cell lung cancer have had limited treatment options after standard therapies. This Phase 3 study represents an important step forward for the field, helping to build the evidence needed to understand whether setidegrasib could offer a potential new approach for this molecularly defined patient population.”

 

Tadaaki Taniguchi, Astellas’ chief research and development officer, said the latest trial reflects the company’s continued development of setidegrasib.

 

“The initiation of this Phase 3 study in NSCLC, our second Phase 3 study of setidegrasib within six months, reflects continued progress in its clinical development. This study will help us understand how setidegrasib’s novel approach to degrading disease-driving KRAS G12D may help address unmet needs for patients with this type of NSCLC. We are grateful to the patients, investigators and study teams making this research possible.”

 

Astellas is also due to present new translational analyses of setidegrasib at the AACR Conference on Pancreatic Cancer in San Diego. The analyses are expected to examine potential mechanisms of response and resistance, as well as possible combination-treatment strategies.

 

The company has said the Phase 3 launches support its broader goal of initiating at least five Phase 3 or pivotal studies by fiscal 2027.

 

However, setidegrasib remains investigational. Its safety and efficacy for the uses being studied have not been established, and there is no guarantee that the drug will ultimately receive regulatory approval or become commercially available for these indications.